psychologywikiaorg-20200213-history
Dopamine receptor D2
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. Function This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia. Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing. Genetics Allelic variants: * A-241G * C132T, G423A, T765C, C939T, C957T, and G1101A * Cys311Ser * -141C insertion/deletion The polymorphisms has been investigated with respect to association with schizophrenia. Some researchers have previously associated the polymorphism Taq 1A (rs1800497) to the DRD2 gene. However, the polymorphism sits in exon 8 of the ANKK1 gene. Ligands Most of the older antipsychotic drugs such as chlorpromazine and haloperidol are antagonists for the dopamine D2 receptor, but are, in general, very unselective, at best selective only for the "D2-like family" receptors and so binding to D2, D3 and D4, and often also to many other receptors such as those for serotonin and histamine, resulting in a range of side-effects and making them poor agents for scientific research. In similar manner, older dopamine agonists used for Parkinson's disease such as bromocriptine and cabergoline are poorly selective for one dopamine receptor over another, and, although most of these agents do act as D2 agonists, they affect other subtypes as well. Several selective D2 ligands are, however, now available, and this number is likely to increase as further research progresses. Agonists * Aplindore - partial agonist * Aripiprazole (Abilify in USA) - partial agonist * GSK-789,472 - mixed D2 partial agonist / D3 antagonist, with good selectivity over other receptors * Talipexole - selective for D2 over other dopamine receptors, but also acts as α2-adrenoceptor agonist and 5HT3 antagonist. * Piribedil - also D3 receptor agonist and α2-adrenergic antagonist * LSD - in vitro, LSD was found to be a partial agonist and potentiates dopamine-mediated prolactin secretion in lactotrophs. LSD is also a 5HT2A agonist. * Pramipexole - also D3, D4 receptor agonist * Quinpirole - also D3 receptor agonist * Quinelorane * Methylphenidate * Salvinorin A - partial agonist. Also k-opioid agonist. * Bromocriptine * Ropinirole Antagonists * L-741,626 (3-4-(4-Chlorophenyl)-4-hydroxypiperidin-l-ylmethyl-1H-indole) - highly selective D2 antagonist * Melperone - D2 antagonist but also 5HT2A antagonist * Risperidone - D2 antagonist but also 5HT2A antagonist * Ziprasidone - D2 antagonist but also 5HT2A antagonist * Raclopride - Radiolabled C11raclopride is commonly employed in Positron emission tomography studies * Clozapine * Quetiapine http://ajp.psychiatryonline.org/cgi/content/abstract/156/6/876 *Domperidone - D2 and D3 antagonist ;D2Sh selective (presynaptic autoreceptors) * Amisulpride (low doses) * UH-232 Interactions Dopamine receptor D2 has been shown to interact with Adenosine A2A receptor, EPB41L1 and PPP1R9B. See also * Dopamine receptor References Further reading * * * * * * * * * * * * * * * * * * }} * External links * * Category:Dopamine] Category:Biology of attention-deficit hyperactivity disorder Category:G protein coupled receptors